Multiscale simulation of the striatal medium spiny neuron (Mattioni & Le Novere 2013)

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Accession:150284
"… We present a new event-driven algorithm to synchronize different neuronal models, which decreases computational time and avoids superfluous synchronizations. The algorithm is implemented in the TimeScales framework. We demonstrate its use by simulating a new multiscale model of the Medium Spiny Neuron of the Neostriatum. The model comprises over a thousand dendritic spines, where the electrical model interacts with the respective instances of a biochemical model. Our results show that a multiscale model is able to exhibit changes of synaptic plasticity as a result of the interaction between electrical and biochemical signaling. …"
Reference:
1 . Mattioni M, Le Novère N (2013) Integration of biochemical and electrical signaling-multiscale model of the medium spiny neuron of the striatum. PLoS One 8:e66811 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
Brain Region(s)/Organism: Striatum;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s): I Na,p; I Na,t; I T low threshold; I A; I K,Ca; I CAN; I Calcium; I A, slow; I Krp; I R; I Q;
Gap Junctions:
Receptor(s):
Gene(s): Kv4.2 KCND2; Kv1.2 KCNA2; Cav1.3 CACNA1D; Cav1.2 CACNA1C; Kv2.1 KCNB1;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s): Synaptic Plasticity; Signaling pathways; Calcium dynamics; Multiscale;
Implementer(s): Mattioni, Michele [mattioni at ebi.ac.uk];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; I Na,p; I Na,t; I T low threshold; I A; I K,Ca; I CAN; I Calcium; I A, slow; I Krp; I R; I Q;
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TimeScales-master
mod
AMPA.mod
bkkca.mod *
cadyn.mod
caL.mod *
caL13.mod *
caldyn.mod
caltrack.mod
can.mod *
caq.mod *
car.mod *
cat.mod *
catrack.mod
GABA.mod *
kaf.mod *
kas.mod *
kir.mod *
krp.mod *
naf.mod *
nap.mod *
NMDA.mod
rubin.mod
skkca.mod
stim.mod *
vecevent.mod
test_input.py
test_vecstim.py
                            
: Calcium ion accumulation with radial and longitudinal diffusion

NEURON {
    THREADSAFE
	SUFFIX catrack
	USEION ca READ cao, cai, ica WRITE cai, ica
	RANGE ica_pmp
	GLOBAL vrat : vrat must be GLOBAL see INITIAL block
	: however TotalBuffer may be RANGE
}

DEFINE Nannuli 4 : must be >=2 (i.e. at least shell and core)

UNITS {
	(molar) = (1/liter)
	(mM) = (millimolar)
	(um) = (micron)
	(mA) = (milliamp)
	FARADAY = (faraday) (10000 coulomb)
	PI = (pi) (1)
	(mol) = (1)
}

PARAMETER {
	DCa = 0.6 (um2/ms)
	k1buf = 100 (/mM-ms) : Yamada et al. 1989
	k2buf = 0.1 (/ms)
	TotalBuffer = 0.003 (mM)
	
	k1 = 1 		(/mM-ms)
	k2 = 0.005	(/ms)
	k3 = 1		(/ms)
	k4 = 0.005	(/mM-ms)

	: to eliminate pump, set TotalPump to 0 in hoc
	TotalPump = 1e-11	(mol/cm2)
}

ASSIGNED {
	diam (um)
	ica (mA/cm2)
	cai (mM)
	vrat[Nannuli] (1) 	: dimensionless
						: numeric value of vrat[i] equals the volume
						: of annulus iof a 1um diameter cylinder
						: multiply by diam^2 to get volume per um length
	Kd (/mM)
	B0 (mM)

	cao	(mM)
	ica_pmp (mA/cm2)
	parea (um)
}

CONSTANT { volo = 1e10	(um2)	}

STATE {
	: ca[0] is equivalent to cai
	: ca[] are very small, so specify absolute tolerance
	ca[Nannuli] (mM) <1e-10>
	CaBuffer[Nannuli] (mM)
	Buffer[Nannuli] (mM)
	
	pump	(mol/cm2)
	pumpca	(mol/cm2)
}

BREAKPOINT { 
	SOLVE state METHOD sparse 
	ica = ica_pmp
}

LOCAL factors_done

INITIAL {
	if (factors_done == 0) { 	: flag becomes 1 in the first segment
		factors_done = 1 		: all subsequent segments will have
		factors() 				: vrat = 0 unless vrat is GLOBAL
	}

	Kd = k1buf/k2buf
	B0 = TotalBuffer/(1 + Kd*cai)

	FROM i=0 TO Nannuli-1 {
		ca[i] = cai
		Buffer[i] = B0
		CaBuffer[i] = TotalBuffer - B0
	}
	
	parea = PI * diam
	pump = TotalPump/(1 + (cai*k1/k2))
	pumpca = TotalPump - pump
}

LOCAL frat[Nannuli] : scales the rate constants for model geometry

PROCEDURE factors() {
	LOCAL r, dr2
	r = 1/2 				: starts at edge (half diam)
	dr2 = r/(Nannuli-1)/2 	: full thickness of outermost annulus,
							: half thickness of all other annuli
	vrat[0] = 0
	frat[0] = 2*r
	FROM i=0 TO Nannuli-2 {
		vrat[i] = vrat[i] + PI*(r-dr2/2)*2*dr2 : interior half
		r = r - dr2
		frat[i+1] = 2*PI*r/(2*dr2) 		: outer radius of annulus
										: div by distance between centers
		r = r - dr2
		vrat[i+1] = PI*(r+dr2/2)*2*dr2 	: outer half of annulus
	}
}

LOCAL dsq, dsqvol 	: can't define local variable in kinetic block
					: or use in COMPARTMENT statement

KINETIC state {
	COMPARTMENT i, diam*diam*vrat[i] {ca CaBuffer Buffer}
	COMPARTMENT (1e10)*parea {pump pumpca}
	COMPARTMENT volo {cao}

	LONGITUDINAL_DIFFUSION i, DCa*diam*diam*vrat[i] {ca}
		:pump
		~ ca[0] + pump <-> pumpca (k1*parea*(1e10), k2*parea*(1e10))
		~ pumpca <-> pump + cao (k3*parea*(1e10), k4*parea*(1e10))
	CONSERVE pump + pumpca = TotalPump * parea * (1e10)
	ica_pmp = 2*FARADAY*(f_flux - b_flux)/parea

	: all currents except pump
		~ ca[0] << (-(ica - ica_pmp)*PI*diam/(2*FARADAY))

	FROM i=0 TO Nannuli-2 {
		~ ca[i] <-> ca[i+1] (DCa*frat[i+1], DCa*frat[i+1])
	}

	dsq = diam*diam

	FROM i=0 TO Nannuli-1 {
		dsqvol = dsq*vrat[i]
		~ ca[i] + Buffer[i] <-> CaBuffer[i] (k1buf*dsqvol, k2buf*dsqvol)
	}

	cai = ca[0]
}


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